I've played a Ravnica game that was pretty successful.
The party consisted of 3 members of Selesnya (a paladin, a wizard, and a cleric), one Boros bro (a sorcerer), one of the Izzet League (an artificer), and my character, a loxodon warlock from the Orzhov (his hook was: "What if the IMF + the Catholic Church were an elephant man?").
It worked pretty well, overall. The Selesnya wizard was brothers with the Boros sorcerer, so they had a family relationship that went in front of their guild differences (and both have some White, so it's not like they were truly far apart). The Izzet artificer and my Orzhov warlock shared a bond something like a silicon valley tech CEO and their investor. The artificer was amoral and focused on just being the special-est smart boy in the room, and my warlock knew this person would be a good source of money for the family, even if it was just selling him insurance.
The threat that united the party was a threat to the whole of Ravnica, and potential apocalypses aren't a bad way to motivate a diverse group to work together. Even the Gruul and the Rakdos want to live, after all. We definitely weren't as close as a typical D&D party (though I think the Selesnya + Boros contingent were all quite friendly), but had a sort of professional interest and courtesy.
The bigwig NPC's made appearances as basically pointers on the plot. One -- the Izzet dragon -- wound up as the chief antagonist. The Selesnya leader made an appearance to help direct us to the goal, and the Rakdos demon was actually the one who could solve our problem (which is fun, since they're very villain-coded, but like I mentioned, nobody wants to DIE).
It was a pretty good success, and I was a big fan of the character I played. They were undead pact, and it was flavored as the spirits and literal bones and tusks of the ancestors. The vibe of the look was like an elephant graveyard turned into a Gothic cathedral. It also let me play against type a bit, since loxodons are typically white or white/green. A white/black kind of vibe on a loxo is a good look, and the character wound up VERY effective (basically a bladelock with a maul made of bones and ghosts and HP comparable to party tanks, and a skelington familiar - flavored as someone who owed my character a debt repaying it after their death - to provide some Help actions).
TL;DR it works fine. Let folks get weird and figure out a plot that puts EVERYONE at risk and your party (assuming the players are chill) will find a reason to work together.